Although rabbits are the only non-primate species reported to acquire systemic HIV-1 infection, the utility of conventional rabbits as models for HIV-1 infection is limited by low efficiency of infection. It was determined that the biology of HIV-1 transmission is closely modeled in rabbits, however. Rabbit offspring born to infected mothers acquired perinatal HIV-1 infections and in some instances infected offspring modeled pediatric cases of AIDS. Infections of primary human lymphocytes with infectious virions produced by infected rabbit cells co-expressing the chemokine surface receptor CCR5 as well as human CD4, which act as receptors for HIV, suggest that a transgenic rabbit model of HIV-1 infection may be feasible. Nevertheless, the scope of work here has been reapportion to place refined emphasis on comparing infection with closely related human T cell leukemia viruses (HTLV-I). The rationale involves investigating biologic consequences of infections with HTLV-I having defined genome differences, as a means of evaluating how different viruses might cause disease or merely cause silent infection. The experimental approach takes advantage of infectious molecular HTLV-I clones, suitable for selected mutagenesis, that were developed with the aid of a well characterized in vivo biologic infection model. Ability to evaluate the consequences of viruses generated by molecular manipulation in rabbits, provides biologic relevance to the comparative studies.